Metabolism of benzo(a)pyrene to carcinogenic 7,8-dihydrodiol 9,10-epoxides has been quantitated in rat hepatocytes, in liver microsomes, and with reconstituted cytochrome P450 and P450-reductase derived from the microsomes. Studies in hepatocytes show that the reactive diol-epoxides readily leave the cell and can modify external DNA almost as readily as nuclear DNA. Modification of nuclear DNA hepatocytes was decreased when the activity of UDP-glucuronyl transferase and sulfotransferase was high, whereas when DNA modification was studied during microsomal metabolism of benzo(a)pyrene, glucuronidation with UDPGA stimulated both DNA modification and diol-epoxide formation. Examination of the kinetics of both processes established that DNA modification (at guanine) and diol-epoxide formation followed the same time course, occurred in a ratio of 1:6, and only became significant when the concentration of benzo(a)pyrene had decreased to the level comparable with that 7,8-dihydrodiol. The stimulatory effect of UDPGA on both processes was time dependent (6-8-fold at 30 min.), and the magnitude was consistent with the effect of UDPGA on the 7,8-diol/benzo(a)pyrene ratio and on the level of inhibitory BP-quinones. The preferential inhibition of 7,8-diol metabolism by BP-quinones seems to derive from a weaker interaction of P450-reductase with the 7,8-diol-P448 complex as compared to the BP-P448 complex.